文献类型：期刊文献

英文题名：Genetically shaping morphology of the filamentous fungus Aspergillus glaucus for production of antitumor polyketide aspergiolide A

作者：Cai, Menghao[1];Zhang, Ying[1];Hu, Wei[1];Shen, Wei[1];Yu, Zhenzhong[1];Zhou, Weiqiang[1];Jiang, Tao[1];Zhou, Xiangshan[1];Zhang, Yuanxing[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2014

卷号：13

外文期刊名：MICROBIAL CELL FACTORIES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000336995700002)】；

基金：This work was supported by National Natural Science Funds of China (31270141, 41306121) and National High Technology Research and Development Program of China (2011AA090702, 2012AA092103, 2012AA092105). We thank Prof. Reinhard Fisher, University of Karlsruhe, for suggestive technical direction.

语种：英文

外文关键词：Filamentous fungi; Aspergillus glaucus; Genetically morphology shaping; Shear stress; Aspergiolide A

摘要：Background: For filamentous fungi, the basic growth unit of hyphae usually makes it sensitive to shear stress which is generated from mechanical force and dynamic fluid in bioreactor, and it severely decreases microbial productions. The conventional strategies against shear-sensitive conundrum in fungal fermentation usually focus on adapting agitation, impeller type and bioreactor configuration, which brings high cost and tough work in industry. This study aims to genetically shape shear resistant morphology of shear-sensitive filamentous fungus Aspergillus glaucus to make it adapt to bioreactor so as to establish an efficient fermentation process. Results: Hyphal morphology shaping by modifying polarized growth genes of A. glaucus was applied to reduce its shear-sensitivity and enhance aspergiolide A production. Degenerate PCR and genome walking were used to obtain polarized growth genes AgkipA and AgteaR, followed by construction of gene-deficient mutants by homologous integration of double crossover. Deletion of both genes caused meandering hyphae, for which, Delta AgkipA led to small but intense curves comparing with Delta AgteaR by morphology analysis. The germination of a second germ tube from conidiospore of the mutants became random while colony growth and development almost maintained the same. Morphology of Delta AgkipA and Delta AgkipA mutants turned to be compact pellet and loose clump in liquid culture, respectively. The curved hyphae of both mutants showed no remarkably resistant to glass bead grinding comparing with the wild type strain. However, they generated greatly different broth rheology which further caused growth and metabolism variations in bioreactor fermentations. By forming pellets, the Delta AgkipA mutant created a tank environment with low-viscosity, low shear stress and high dissolved oxygen tension, leading to high production of aspergiolide A (121.7 +/- 2.3 mg/L), which was 82.2% higher than the wild type. Conclusions: A new strategy for shaping fungal morphology by modifying polarized growth genes was applied in submerged fermentation in bioreactor. This work provides useful information of shaping fungal morphology for submerged fermentation by genetically modification, which could be valuable for morphology improvement of industrial filamentous fungi.